Reactivity toward oxygen of isobenzofuranyl radicals: Effect of nitro group substitution

Article abstract of DOI:10.1021/ol034307p

(Matrix presented) The presence of a nitro group in the p-phenyl position dramatically slows down the oxygenation of isobenzofuranyl radicals. However, both unsubstituted and m-substituted phenyl rings have no appreciable influence on the reactivity toward oxygen. Spin delocalization on the nitro group is proposed to explain the stability of the carbon-centered radical generated.

Full text of DOI:10.1021/ol034307p

ORGANIC
LETTERS
2003
Vol. 5, No. 9
1515-1518
Reactivity toward Oxygen of
Isobenzofuranyl Radicals: Effect of
Nitro Group Substitution
Enrique Font-Sanchis, Carolina Aliaga, Raecca Cornejo, and J. C. Scaiano*
Department of Chemistry, UniVersity of Ottawa, Ottawa, Ontario, Canada K1N 6N5
tito@photo.chem.uottawa.ca
Received February 20, 2003
ABSTRACT
The presence of a nitro group in the p-phenyl position dramatically slows down the oxygenation of isobenzofuranyl radicals. However, both
unsubstituted and m-substituted phenyl rings have no appreciable influence on the reactivity toward oxygen. Spin delocalization on the nitro
group is proposed to explain the stability of the carbon-centered radical generated.
Benzofuranones and isobenzofuranones (phthalides) have
been used as stabilizers to prevent thermal and oxidative
decomposition during the processing of polymers at high
temperatures.1,2 In fact, some of these benzofuranones have
been found to be relatively good hydrogen donors, and the
carbon-centered radicals generated from them present low
reactivity toward oxygen, showing typical properties of chain
breaking antioxidants.
delocalization on nitrogen has been proposed to be the most
important factor to explain this unusual behavior.
On the other hand, it is known that the reactivity of
benzylic radicals toward oxygen is influenced by the presence
of substituents in the aromatic ring.6 Thus, the presence of
para electron-donating groups such as methoxy or methyl
increases slightly the reactivity with oxygen in comparison
with the parent benzyl radical. However, in the presence of
strong para electron-withdrawing groups such as cyano or
nitro, the reactivity with oxygen can be attenuated by a factor
of 3. Further, depending on the position of the substituent
in the aromatic ring the reactivity of carbon-centered radicals
with oxygen can be altered. For example, m-cyanobenzyl
radical is as reactive as the benzyl radical.
We have proposed that five parameters can be used to
rationalize the attenuated reactivity of carbon-centered
radicals toward oxygen: (a) benzylic resonance stabilization;
(b) favorable stereoelectronic effects; (c) unpaired spin
delocalization on heteroatoms (particularly oxygen); (d)
electron-withdrawing effects; and (e) steric effects.3,4
An interesting example is the diphenylpicryl hydrazyl
radical (DPPH), a commercially available nitrogen-centered
radical that is stabilized by an aromatic ring that bears three
nitro groups in the ortho and para positions. It is clear that
steric and electronic effects due to the presence of the nitro
groups play a role in determining the stability of this radical.
We have recently reported on the importance of electronic
effects on some nitrile-derived carbon-centered radicals to
explain their low reactivity with oxygen.5 In fact, spin
(1) Krohnke, C.; Brede, O.; Epacher, E.; Turcsanyi, B.; Pukanszky, B.
Polym. Prepr. 2001, 42, 388.
(2) Nesvada, P. E., Sr.; Krohnke, Ch.; Zingg, J. Ger. Offen. 4432732,
1984; Chem. Abstr. 1995, 123, 55685.
(3) Scaiano, J. C.; Martin, A.; Yap, G. P. A.; Ingold, K. U. Org. Lett.
2000, 2, 899.
(4) Bejan, E. V.; Font-Sanchis, E.; Scaiano, J. C. Org. Lett. 2001, 3,
4059.
(5) Font-Sanchis, E.; Aliaga, C.; Focsaneanu, K.-S.; Scaiano, J. C. Chem.
Commun. 2002, 1576.
(6) Tokumura, K.; Ozaki, T.; Nosaka, H.; Saigusa, Y.; Itoh, M. J. Am.
Chem. Soc. 1991, 113, 4974.
10.1021/ol034307p CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/09/2003

In this context, we now report the generation and reactivity
with oxygen of the radicals derived from isobenzofuranone
compounds in Scheme 1. We selected these molecules to
Table 1. Absorption of the Radicals, Rate Constants for the
Reactions of Cumyloxyl/tert-Butoxyl Radicals with Hydrogen
Donors, and Reactivity toward Oxygen
alkoxyl radical
rate constant
radical
wavelength
max, nm
reactivity
with
oxygena
Scheme 1. Isobenzofuranones Studied and Related Compounds
substrate
(106 M-1 s-1
)
HP-1364
12.4b
51c
340
400
360, 525
360
340
340, 380
340, 580
340
no
no
2-coumaranone4
1
2
3
4
5
6
7
2.07c
yes
(no)d
yes
yes
no
5.35e
2.83e
3.77e
3.01e
2.70e
yes
yes
340
a Based of laser flash photolysis work in a 100-µs time scale. b Obtained
by laser flash photolysis of dicumyl peroxide. c Obtained by laser flash
photolysis of di-tert-butyl peroxide. d This measurements are difficult due
to potential interference of Br2•- at 360 nm. There are also poorly resolved
absorbances in the 500-600 nm range; these are normal for a radical with
this structure. e Obtained from product studies with cumyl hyponitrite as
the source of cumyloxyl radicals.
bands were detectable between 300 and 700 nm, indicating
a low contribution of the carbonyl group to the absorption
of the radical. Further, the signal for the radical from 3 was
quenched by oxygen with a rate constant of 7.2 × 108 M-1
s-1. This is about a million times faster than the isomeric
radical from 2-coumaranone.
Benzyl radicals are readily quenched by paramagnetic
substrates such as nitroxide radicals (the rate constants for
these reactions are frequently ∼108 M-1 s-1 in acetonitrile).9
Thus, the rate constants of the radicals generated from 3 and
the HP-136 toward 2,2,5,5-tetramethylpiperidin-1-oxyl
(TEMPO) were obtained from the transient decay at different
TEMPO concentrations in mixtures of benzene/di-tert-butyl
peroxide (1/1 v/v). The values obtained are 1.77 × 107 and
1.35 × 105 M-1 s-1, respectively. Clearly, the benzofuranone
structure leads to a more stable, and therefore less reactive
radical.
From the above results, it seems that the contribution of
the resonance form centered on oxygen is decisive to explain
the lack of reactivity of the benzofuranone structure toward
oxygen. In fact, spin density calculation data10 for the radical
from phthalide 1 show higher spin density located on the
benzylic carbon atom (52.4%) than for the radical from
2-coumaranone (45.3%).
compare their reactivity toward oxygen with those previously
reported for benzofuranones4 and to establish the importance
of electron-withdrawing effects due to the presence of nitro
or trifluoromethyl groups.
The radicals were generated from the corresponding
precursors by laser excitation of di-tert-butyl peroxide in
benzene 50% (v/v), using 355-nm laser pulses (radical
absorption maxima are given in Table 1). The tert-butoxyl
radicals abstract the benzylic hydrogen to produce carbon-
centered radicals and tert-butyl alcohol. The growth of the
radical signal reflects the H-abstraction and other forms of
decay of tert-butoxyl such as reaction with the solvent and
â-cleavage.7
Under a nitrogen atmosphere the radical generated from
3H-isobenzofuran-1-one (1) absorbs at 360 and 525 nm. The
visible band is more intense than in the case of the benzyl
radical; this enhancement is probably due to the presence of
heteroatoms. A similar behavior has been previously de-
scribed for the 2-coumaranone radical; however, in this case
the maximum was detected at 400 nm and the intensity of
the band was far greater than that in the case of the radical
from 1. When the same experiments are carried out in
oxygen-saturated samples the transient is totally quenched.
The photolysis of di-tert-butyl peroxide under nitrogen in
the presence of 3-phenyl-3H-isobenzofuran-1-one (3) (0.05
M) yields a transient with maximum at 340 nm; this band is
quite similar to that for the diphenylmethyl radical.8 No other
If we assume that the spin density at the benzylic position
is key to the coupling reaction of benzyl radical and
(8) Scaiano, J. C.; Tanner, M.; Weir, D. J. Am. Chem. Soc. 1985, 107,
4396.
(9) Beckwith, A. L. J.; Bowry, V. W.; Ingold, K. U. J. Am. Chem. Soc.
1992, 114, 4983.
(10) Spin density calculations were calculated by Density Functional
Theory. Electronic structures of the radical molecules were calculated with
use of the Spartan software package (V.5.0.3, Wavefunction, Inc. Irvine).
The molecular structures were optimized employing a split-valence basis
with a single set of polarization functions added to each atom (DN**). A
gradient-corrected functional combining Becke-Perdew as the exchange-
correlation functional (BP86) was chosen. For more details see the
Supporting Information.
(7) Paul, H.; Small, R. D.; Scaiano, J. C. J. Am. Chem. Soc. 1978, 100,
4520.
1516
Org. Lett., Vol. 5, No. 9, 2003

molecular oxygen, the introduction of electron-withdrawing
groups could reduce the reactivity with oxygen of the carbon-
centered radical. With this aim, we generated and studied
the radicals from molecules 2 and 4-7.
photolysis is carried out in benzene, together with the band
at 360 nm we observed a second band at 550 nm with a
lifetime around 2 µs. This transient can be assigned to the
well-known bromine radical-benzene complex.13 Further,
spin density calculations for the radical from 6-nitrophthalide
(2) show less spin density located on the benzylic carbon
atom than for the radical from 1.
In the presence of a nitrogen atmosphere, the abstraction
of the benzylic hydrogen by tert-butoxyl radicals in the case
of 3-(3-nitro-phenyl)-3H-isobenzofuran-1-one (4) (0.004 M)
produces a transient with maxima at 340 and 380 nm (Figure
1, top); this transient is readily quenched by oxygen.
However, LFP of the peroxide in the presence of 3-(4-
nitro-phenyl)-3H-isobenzofuran-1-one (5) (0.004 M) gener-
ates a transient with maxima at 340 and 580 nm (Figure 1,
bottom) that is not affected by the presence of oxygen (Figure
2). The intense band observed at 580 nm might indicate the
Figure 1. Top: Transient absorption spectra recorded following
355-nm laser excitation of a 0.004 M sample containing 3-(3-
nitrophenyl)-3H-isobenzofuran-1-one (4) in benzene/di-tert-butyl
peroxide (50/50) under nitrogen, (b) 7.84 µs and (O) 31 µs after
the laser pulse. Bottom: Transient absorption spectra recorded
following 355-nm laser excitation of a 0.004 M sample containing
3-(4-nitrophenyl)-3H-isobenzofuran-1-one (5) in benzene/di-tert-
butyl peroxide (50/50) under nitrogen, (b) 1.08 µs and (O) 7.60
µs after the laser pulse.
The photolysis of di-tert-butyl peroxide in the presence
of 6-nitrophthalide does not produce good signals that might
be used to monitor its formation. On the other hand, it is
known that photolysis of benzylhalide compounds leads to
the homolytic cleavage of the C-X bond to generate benzylic
radicals.11 Thus, the radical from 6-nitrophthalide is generated
by laser flash photolysis (LFP) of 2 (0.001 M) at 355 nm in
benzene or acetonitrile. The radical generated in acetonitrile
shows a broad band around 360 nm that does not decay
completely after 100 µs. Monitoring at 360 nm,12 the
comparison of nitrogen- and oxygen-saturated samples shows
that the signal decay is not influenced by oxygen. When the
Figure 2. Transient kinetic trace recorded following 355-nm laser
excitation of a sample containing a 0.004 M sample of 3-(4-
nitrophenyl)-3H-isobenzofuran-1-one (5) in benzene/di-tert-butyl
peroxide (50/50) under nitrogen (b) and oxygen (2) at 340 (top)
and 580 nm (bottom).
contribution of the nitro group to the chromophore. A similar
absorption spectrum has been previously reported for the
p-nitrobenzyl radical.14
The absorption spectra and reactivity toward oxygen of
the radicals generated from the trifluoromethyl compounds
6 and 7 are similar to that observed for the radical from 3.
(11) Miranda, M. A.; Perez-Prieto, J.; Font-Sanchis, E.; Scaiano, J. C.
Acc. Chem. Res. 2001, 34, 717.
(12) These signals may be somewhat contaminated by Br2•- that absorbs
in the same region. It is clear, however, that the dominant contribution is
•-
from the phthalide radical, since Br2 is shorter lived, and the 360-nm
signal is also observed in benzene, where bromine atoms have a different
fate: Hug, G. L. Optical Spectra of Nonmetallic Inorganic Transient Species
in Aqueous Solution; National Bureau of Standards: Washington, DC, 1981;
Vol. NSRDS-NBS 69.
(13) McGimpsey, W. G.; Scaiano, J. C. Can. J. Chem. 1988, 66, 1474.
(14) Kita, F.; Adam, W.; Jordan, P.; Nau, W. M.; Wirz, J. J. Am. Chem.
Soc. 1999, 121, 9265.
Org. Lett., Vol. 5, No. 9, 2003
1517

A good antioxidant needs to be a good hydrogen donor.
Thus, we also examined the reactivity of 3-7 toward
cumyloxyl radicals by the thermolysis of di-R-cumyl hy-
ponitrite, where the rate constants are based on product
studies (acetophenone vs cumyl alcohol).15,16 The isobenzo-
furanones studied are good hydrogen donors, but their
reactions are somewhat slower than in the case of benzo-
furanones (e.g., HP-136 and 2-coumaranone). From an
oversimplified approach, in the latter case one can write
resonance structures placing the spin on oxygen without
affecting ring aromaticity, something that is also reflected
in the spin density calculations.
In summary, it is clear that the presence of a nitro group
in the p-phenyl position slows down the oxygenation of
isobenzofuranyl radicals. However, meta substituents have
no appreciable influence on the reactivity toward oxygen.
These results, together with the fact that the radicals derived
from trifluoromethyl compounds 6 and 7 react with oxygen,
show the importance of spin delocalization on a heteroatom
(oxygen in this case) to explain the stability of the carbon-
centered radical generated. Clearly the benzofuranone struc-
ture is better than the isobenzofuranone in stabilizing the
carbon radical center toward reaction with oxygen. This
should be attributed to resonance stabilization effects, since
steric and electron-withdrawing effects should be comparable.
Even addition of a phenyl ring (as in 3) is not enough to
prevent reaction, but rather the strong electron-withdrawing
effect from a p-nitro substituent is needed.
Acknowledgment. J.C.S. thanks the Natural Sciences and
Engineering Research Council of Canada and Imperial Oil
Canada for generous support. E.F.S. thanks the Spanish
Ministry of Education for a grant.
Supporting Information Available: Experimental de-
tails, methodology used for determining H-abstraction con-
stants, and spin density distribution for radicals. This material
is available free of charge via the Internet at http://pubs.acs.org.
(15) Avila, D. V.; Brown, C. E.; Ingold, K. U.; Lusztyk, J. J. Am. Chem.
Soc. 1993, 115, 466.
(16) Font-Sanchis, E.; Aliaga, C.; Bejan, E. V.; Cornejo, R.; Scaiano, J.
C. J. Org. Chem. 2003, in press.
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